Polyamidoamine (PAMAM) dendrimers, which consist of a central core, regularly branched monomeric building blocks, and many surface terminal groups, are considered to be good candidate nanoparticles for use as anti-tumor therapeutics and drug delivery due to their controlled mass, surface valency, and surface functionality. To investigate the effect on pore formation of the dendrimer properties (molecular size and shape, charge density, and concentration) and solution conditions (temperature and salt concentration), and to test the ability of coarse-grained (CG) models to predict experimentally measured dendrimer-bilayer properties, we have performed molecular dynamics (MD) simulations of differently acetylated G5 and G7 PAMAM dendrimers in DMPC bilayers with explicit water using the CG model developed by Marrink et al. (J. Phys. Chem. B. 2007, 111, 7812) with inclusion of long-range electrostatics. When initially clustered together near the bilayer, neutral acetylated dendrimers aggregate, whereas cationic un-acetylated dendrimers do not aggregate, but separate from each other, similar to observations from atomic force microscopy by Mecke et al. (Chem. Phys. Lipids. 2004, 132, 3). The bilayers interacting with un-acetylated dendrimers of higher concentration are significantly deformed and show pore formation on the positively curved portions, while acetylated dendrimers are unable to form pores. Un-acetylated G7 dendrimers bring more water molecules into the pores than do un-acetylated G5 dendrimers. These results agree qualitatively with experimental results showing that significant cytoplasmic-protein leakage is produced by un-acetylated G7 dendrimers at concentrations as low as 10 nM, but only at a much higher concentration of 400 nM for un-acetylated G5 dendrimers (Bioconj. Chem. 2004, 15, 774). At higher salt concentration (~500mM NaCl) or lower temperature (277 K), un-acetylated dendrimers do not insert into the bilayer, which again corresponds to the experimental results. To investigate the effect of molecular shape, we also performed MD simulations of multiple copies of poly-L-lysine (PLL) in DMPC bilayers. Membrane disruption is enhanced at higher concentrations and charge densities of both spheroidally shaped dendrimers and linear PLL polymers, in qualitatively agreement with experimental studies by Hong et al. (Bioconjugate Chem. 2006, 17, 728). However, larger molecular size enhances membrane disruption and pore formation only for dendrimers and not for the linear PLL. Despite more intimate electrostatic interactions of linear molecules than are possible for spheroidal dendrimers, only the dendrimers were found to perforate membranes, apparently because they cannot spread onto a single leaflet, and so must penetrate the bilayer to get favorable electrostatic interactions with head groups on the opposite leaflet. These results indicate that a relatively rigid spheroidal shape is more efficient than a flexible linear shape in increasing membrane permeability. These good qualitative agreements indicate that the effect on pore formation of the molecular size and shape, charge density, and concentration of large nanoparticles can be studied through coarse-grained MD simulations, provided that long-range electrostatic interactions are included.